New methods are needed to produce pharmaceutical quality proteins for therapeutic use in humans on a large scale. Many heritable metabolic storage disorders of humans are potentially treatable by supplementation with exogenously produced enzymes. For example, Gaucher's disease is caused by genetic deficiencies in the enzyme glucocerebrosidase and can be successfully treated by enzyme replacement therapy. However, cost and availability of the enzyme limit access to treatment. Plants are relatively unexplored production hosts for cost-effective biosynthesis of human proteins. Using recently developed transient expression vectors based on tobacco mosaic virus, we will examine the feasibility of producing custom-designed proteins in plants using glucocerebrosidase as a test enzyme. These vectors allow both high levels of expression and rapid cycles of testing and modification of the enzyme. If the enzyme produced in plants shows catalytic activity toward the accumulating glucocerebroside, we can rapidly test experimental alterations to facilitate purification, stability, and targeting of the enzyme to lipid storing cells. The long-term objectives are to develop methods for producing copious amounts of glucocerebrosidase and other human enzymes for routine therapeutic treatments. Using this method, custom peptide synthesis could be designed for individuals that may be intolerant to the wild type enzyme. PROPOSED COMMERCIAL APPLICATION: The inexpensive biomass and economy of scale of plant growth offer the potential to drastically reduce the cost of manufacture of human proteins. There is an ever increasing commercial demand for these proteins in therapeutic applications.